Defects in skin gamma delta T cell function contribute to delayed wound repair in rapamycin-treated mice.
Defects in skin gamma delta T cell function contribute to delayed wound repair in rapamycin-treated mice.
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DOI：
10.4049/jimmunol.181.6.3974
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发表时间：
2008-09-15
期刊：
影响因子：
--
通讯作者：
Jameson JM
中科院分区：
文献类型：
--
作者：
Mills RE;Taylor KR;Podshivalova K;McKay DB;Jameson JM
组织修复正常程序的中断可导致伤口愈合不良，这扰乱了屏障组织如皮肤的完整性。这种伤口修复缺陷发生在接受免疫抑制药物雷帕霉素（西罗莫司）治疗的移植受者身上。上皮内淋巴细胞，如皮肤中的γδT细胞，通过产生细胞因子和生长因子介导组织修复。在伤口修复的小鼠模型中分析了雷帕霉素治疗期间皮肤驻留T细胞发挥功能的能力。雷帕霉素处理使皮肤γδ T细胞不能增殖、迁移和产生正常水平的生长因子。观察到的皮肤γδ T细胞功能的损害与雷帕霉素对哺乳动物雷帕霉素靶蛋白（mTOR）的抑制作用直接相关。用雷帕霉素处理的皮肤γδ Τ细胞对IL-2刺激是难治的，并且试图通过经历自噬在细胞因子和生长因子信号传导不存在的情况下存活。在雷帕霉素处理的小鼠中，通过添加皮肤γδ T细胞产生的因子，胰岛素样生长因子-1，可以恢复正常的伤口闭合。这些研究不仅揭示了mTOR是γδ T细胞功能的主要调节因子，而且还为雷帕霉素给药期间发生的对不愈合伤口的易感性增加提供了一种新的机制。这是作者制作的手稿版本，已被《免疫学杂志》（The JI）接受出版。美国免疫学家协会(AAI)JI的出版商拥有本手稿的版权。这一版本的手稿尚未由联合执行进行复制编辑或编辑校对;因此，它可能与联合执行发表的最后版本（在线和印刷版）不同。AAI（JI）对作者制作的手稿版本或美国国立卫生研究院或任何其他第三方从中衍生的任何版本中的错误或遗漏不承担责任。记录的最终可引用版本可在www.jimmunol.org上找到。
Disruptions in the normal program of tissue repair can result in poor wound healing, which perturbs the integrity of barrier tissues such as the skin. Such defects in wound repair occur in transplant recipients treated with the immunosuppressant drug rapamycin (sirolimus). Intraepithelial lymphocytes, such as γδT cells in the skin, mediate tissue repair through the production of cytokines and growth factors. The capacity of skin-resident T cells to function during rapamycin treatment was analyzed in a mouse model of wound repair. Rapamycin treatment renders skin γδ T cells unable to proliferate, migrate and produce normal levels of growth factors. The observed impairment of skin γδ T cell function is directly related to the inhibitory action of rapamycin on mammalian target of rapamycin (mTOR). Skin γδ T cells treated with rapamycin are refractory to IL-2 stimulation and attempt to survive in the absence of cytokine and growth factor signaling by undergoing autophagy. Normal wound closure can be restored in rapamycin-treated mice by addition of the skin γδ T cell-produced factor, insulin-like growth factor-1. These studies not only reveal that mTOR is a master regulator of γδ T cell function but also provide a novel mechanism for the increased susceptibility to nonhealing wounds that occurs during rapamycin administration. This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI, holds the copyright to this manuscript. This version of the manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may differ from the final version published in The JI (online and in print). AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the U.S. National Institutes of Health or any other third party. The final, citable version of record can be found at www.jimmunol.org.
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DOI：
10.1084/jem.20042020
发表时间：
2005-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.3
作者：
Gonzalez, J;Harris, T;Prystowsky, MB
通讯作者：
Prystowsky, MB
影响因子：
5.3
作者：
Fingar, DC;Richardson, CJ;Blenis, J
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Blenis, J
影响因子：
0.9
作者：
Ekici, Y.;Emiroglu, R.;Haberal, M.
通讯作者：
Haberal, M.
影响因子：
5.8
作者：
Born, W K;Lahn, M;Gelfand, E W
通讯作者：
Gelfand, E W